Ana Ivanovic's frustrating run continued on Monday as she became the first major women's casualty of the US Open, eliminated by Dominika Cibulkova 6-3 3-6 6-3.
Since her run to the French Open semi-finals, world number seven Ivanovic has only won four WTA Tour-level matches, and her defeat at the hands of Cibulkova is another major disappointment.
Ivanovic's first-round grand-slam exit is her second of 2015 after suffering the same fate at the Australian Open, while she was a second-round loser at Wimbledon.
The 27-year-old was not the only seed to fall on Monday, with Karolina Pliskova (eighth), Carla Suarez Navarro (10th), Jelena Jankovic (21st), Sloane Stephens (29th) and Svetlana Kuznetsova (30th) all sent packing on the opening day.
Rising star Pliskova crashed out in a 6-2 6-1 defeat to Anna Tatishvili.
Pliskova tallied 18 unforced errors to just nine winners throughout the match against the American qualifier in New York.
Suarez Navarro lost her clash 6-1 7-6 (7-5) to Denisa Allertova.
Jankovic suffered a 2-6 7-5 6-3 loss at the hands of Oceane Dodin.
Coco Vandeweghe ousted fellow American Sloane Stephens 6-4 6-3, while Kuznetsova was defeated by Kristina Mladenovic 6-3 7-5.
Serena Williams was on court for just 30 minutes as she opened her Grand Slam bid in comfortable fashion at Flushing Meadows.
The world number one, aiming to become the first player since Steffi Graf in 1988 to win all four grand slams in a calendar year, eased past Russian Vitalia Diatchenko in the first round.
Williams led 6-0 2-0 when Diatchenko retired, having struggled throughout with injury.
Sister Venus also advanced to the second round via a 6-4 6-7 (7-9) 6-3 victory over Monica Puig.
Polish 15th seed Agnieszka Radwanska eased past an error-riddled Katerina Siniakova 6-2 6-3, however sister Urszula lost to countrywoman Magda Linette 7-6 (7-3) 6-0.
British number one Heather Watson suffered a fifth consecutive first-round loss in New York, beaten 7-6 (7-3) 7-6 (7-0) by Lauren Davis.
Canadian 25th seed Eugenie Bouchard, who has failed to build on her breakout season in 2014, broke serve five times en route to a 6-4 6-3 win against Alison Riske.
Swiss starlet and 12th seed Belinda Bencic crushed Sesil Karatantcheva 6-1 6-2, Madison Keys eased past Klara Koukalova 6-2 6-4, Ekaterina Makarova accounted for Teliana Pereira 6-3 6-3 and 17th seed Elina Svitolina downed Elizaveta Kulichkova 6-1 6-4.
Kaia Kanepi saw off Anna-Lena Friedsam 6-1 6-1, Madison Brengle outlasted Saisai Zheng 6-2 5-7 7-5, 31st seed Anastasia Pavlyuchenkova was a 6-4 7-5 winner against Magdalena Rybarikova, Kiki Bertens overcame Mirjana Lucic-Baroni 3-6 6-4 6-2 and Roberta Vinci trumped Vania King 6-4 6-4.
Bethanie Mattek-Sands advanced via a 6-4 6-3 victory against Kateryna Kozlova, Daniela Hantuchova lost 6-3 6-3 to Misaki Doi and teenager Daria Kasatkina condemned Daria Gavrilova to a 6-2 4-6 7-5 defeat.
Casey Dellacqua went down 7-5 6-2 to Anett Kontaveit, there was a 6-2 6-2 win for Bojana Jovanovski against Lara Arruabarrena, Irina Falconi triumphed 6-4 6-2 over Samantha Crawford, while Polona Hercog survived a late rally to beat Zarina Diyas 6-2 7-5.
Jessica Pegula stunned Alison Van Uytvanck 7-5 6-3, Mariana Duque-Marino swept aside 16-year-old Sofia Kenin 6-3 6-1, Andreea Mitu fell to Tereza Smitkova 7-6 (7-4) 6-2 and Ana Konjuh eliminated Tatjana Maria 6-4 6-4.